An acquired unresponsiveness to Pseudomonas aeruginosa antigens has been identified in cystic fibrosis patients with low case history scores. In vitro lymphocyte proliferative responses to pseudomonas are depressed or absent in these patients, while responses to mitogens (e.g. phytohemagglutinin and Concanavalian A) and other bacterial antigens (S. aureus, S. pyogenes and H. influenzae) remain normal or are elevated. This research project is directed toward the following questions: a) What factors (i.e. cellular or humoral) are responsible for unresponsiveness to pseudomonas in CF lymphocytes; b) Is unresponsiveness a unique feature of chronic pseudomonas pulmonary infection in CF; c) Is unresponsiveness to pseudomonas of pathophysiologic significance; d) Can the response to pseudomonas be restored or increased. Studies will be undertaken to further elucidate the roles of plasma factors, T-lymphocytes, B-lymphocytes, macrophages and their soluble products in the immunologic response to pseudomonas in CF and their possible significance in the pathophysiology of chronic pseudomonas infection in these patients.